Unique Statistics:

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

Abstract

A 61-year old man was admitted with a 2-month history of skin rash, and proteinuria and intermittent hemoptysis for 2 weeks. The patient had developed circular erythema and blisters all over the body with scab formation. Edema of the legs and eyelids appeared 2 weeks prior to admission. Kidney biopsy showed membranous nephropathy (phase II) with focal segmental mesangial proliferation and deposits of IgG along the GBM. Skin biopsy demonstrated IgG deposits in the epidermal basement membrane zone. The simultaneous development of a rare renal and skin autoimmune disorder, resulting from non-cross-reactive autoantibodies, suggests that a common triggering event could be responsible for the autoimmune injury. This patient with bullous pemphigoid was treated with corticosteroids, which were tapered to an acceptable and effective maintenance dose following treatment with intravenous cyclophosphamide.

INTRODUCTION

Bullous pemphigoid (BP) is a skin disease that causes blisters. It affects mainly people over 60 years of age. We report a patient with bullous pemphigoid who presented with cutaneous lesions and nephrotic syndrome. Renal pathological diagnosis was membranous nephropathy (phase II) with focal segmental mesangial proliferation. Treatment with corticosteroids and other immunossupressives effectively controlled symptoms.

CASE REPORT

A 61-year old man was admitted with a 2-month history of skin rash and proteinuria and intermittent hemoptysis for 2 weeks. The patient had developed circular erythema and blisters all over the body with scab formation. Edema of the legs and eyelids appeared 2 weeks prior to admission. The patient was previously well, was not on medication before the skin eruption, had no systemic signs, was afebrile and normotensive. There was generalised circular erythema and blisters with scabs throughout the body. The blisters were firm and dome-shaped, and ranged from 10 mm to 20 mm (Fig. 1). Palpebral and pedal edema and congested throat were present. The white blood cell count was 6.2 ×109/L, with a differential of 78% N, 17% L and 5% M and a platelet count of 2.06 × 1011/L. Urinary RBC of 0-2/HP and 24 h-urinary protein of 7.7 g was present. Serum IgG, IgA and IgM were 7.98 g/L, 1.37g/L, and 1.63 g/L respectively. C3, C4, ALT and AST were normal. The ESR was 60 mm/h. Serum Albumin/Globulin 18.9/27.4 g/L, total cholesterol CHO 11.23 mmol/L, TG 2.55 mmol/L and LDL-C 8.94 mmol/L.

Fig. (1).

Bullous pemphigoid; cutaneous biopsy HE stain (10X).

Fig. (2).

Blisters were seen under the cutis. The capillaries of the
upper dermis were dilated and congested, and infiltrated by
eosinophils, lymphocytes and plasma cells.

He was treated with prednisone acetate 60 mg poqd for 8-weeks, before being tapered off, and dipyridamole, benazepril hydrochloride and alprostadil. Plasma albumin increased to 22.7 g/L and the 24 h-urinary protein decreased to 5.28 g after treatment. Intravenous cyclophosphamide 1.0 g/month was given at this time and after two months,

DISCUSSION

Bullous pemphigoid (BP) is a subepidermal autoimmune bullous skin disease. It is associated with autoantibodies directed against the BP antigens 180 (BPAG2) and BP230 (BPAG1). The pathogenicity of anti-BP180 antibodies has been convincingly demonstrated in animal models. The clinical features of BP are extremely pleomorphic. The diagnosis of BP critically relies on immunopathologic findings. The recent development of novel enzyme-linked immunosorbent assays has allowed the detection of circulating autoantibodies with relatively high sensitivity and specificity [1].

It is mediated by circulating antibodies directed against two hemidesmosomal proteins of the dermal epidermal junction: BPAG1 and BPAG2. Clinical features consist of pruritus and tense blisters usually surrounded by erythema. Blisters sometimes evolve to erosions, become haemorrhagic and can progress to large erosive areas. Lesions heal without scarring. Lesions are symmetrically located on the thighs, legs, trunk and arms. Mucous membranes are usually uninvolved. Histological examination of a skin biopsy specimen shows a subepidermal blister with eosinophils within the blister and the superficial dermis. Direct immunofluorescence shows linear IgG and/or C3 deposits along the dermal epidermal junction [2].

Proinflammatory cytokines such as TNF-α, IL-6 and Th1-like cytokines (IL-2 and INF-γ) are not detected, neither as proteins nor as mRNA. Since IL-4 and IL-5 are important in eosinophil chemoattraction, maturation and functional activity, the presence of IL-4 and IL-5 in BP suggest that these cytokines could be important in the pathogenesis of the disease [3].

The patient had deposits of IgG in the kidney and the skin, along the GBM and the epidermal basement membrane zone respectively. The patient's autoantibodies immunoblotted the intracellular domain but not the extracellular domain of BP180. Reactivity of the patient's IgG with BP180 was found only in the unbound fraction of the serum. The simultaneous development of a rare renal and skin autoimmune disorder, resulting from non-cross-reactive autoantibodies, suggests that a common triggering event could be responsible for the autoimmune injury [4].

In bullous pemphigoid, azathioprine and mycophenolate mofetil seem to be equally effective when used in combination with oral corticosteroids, but mycophenolate mofetil is less myelosuppressive and hepatotoxic. Cyclophosphamide still has a place in the treatment of severe relapsing autoimmune bullous diseases. Several pulsed cyclophosphamide regimens have, therefore, been developed and are reported to be effective in severe forms of pemphigus. Randomized controlled studies are needed to compare the efficacy and safety of cyclophosphamide with newer treatment options, such as rituximab and immunoapheresis, and to define optimal dose ranges and duration of available immunosuppressive treatments in different stages of autoimmune bullous diseases [5].

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

Indexing Agencies

Press Release

Join Our Editorial Board

News release date: March 29, 2018

Description:

The Open Urology & Nephrology Journal is an Open Access online journal, which publishes research articles, reviews, letters, case reports and guest-edited single topic issues in all areas of urology and nephrology. Bentham Open ensures speedy peer review process and accepted papers are published within 2 weeks of final acceptance.

The Open Urology & Nephrology Journal is committed to ensuring high quality of research published. We believe that a dedicated and committed team of editors and reviewers make it possible to ensure the quality of the research papers. The overall standing of a journal is in a way, reflective of the quality of its Editor(s) and Editorial Board and its members.

The Open Urology & Nephrology Journal is seeking energetic and qualified researchers to join its editorial board team as Editorial Board Members or reviewers.

The essential criteria to become Editorial Board Members of The Open Urology & Nephrology Journal are as follows:

Experience in urology and nephrology with an academic degree.

At least 20 publication records of articles and /or books related to the field of urology and nephrology or in a specific research field.

Proficiency in English language.

The Roles of Editorial Board Member are to:

Offer advice on journals’ policy and scope.

Submit or solicit at least one article for the journal annually.

Contribute and/or solicit Guest Edited thematic issues to the journal in a hot area (at least one thematic issue every two years).

Peer-review of articles for the journal, which are in the area of expertise (2 to 3 times per year).

If you are interested in becoming our Editorial Board member, please submit the following information to info@benthamopen.com. We will respond to your inquiry shortly.

Email subject: Editorial Board Member Application

Your name

Email address

Telephone

City, State, Country

Name of your institution

Department or Division

Website of institution

Your title or position

Your highest degree

Complete list of publications and h-index

Interested field(s)

Testimonials

"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."

. —Daniel Pesut. (Indiana University School of Nursing, USA).

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."

. —Patrice Talaga. (UCB S.A., Belgium).

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."

. —Jeffrey M. Weinberg. (St. Luke's-Roosevelt Hospital Center, USA).

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."

. —Debomoy K. Lahiri. (Indiana University School of Medicine, USA).

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."

. —Robert Looney. (Naval Postgraduate School, USA).

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."

. —Richard Reithinger. (Westat, USA).

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."

. —J. Ferwerda. (University of Oxford, UK).

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."

. —Sean L. Kitson. (Almac Sciences, Northern Ireland).

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."

. —Hubert Wolterbeek. (Delft University of Technology, The Netherlands).

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."

. —Alessandro Laviano. (Sapienza - University of Rome, Italy).

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."

. —Philippe Hernigou. (Paris University, France).

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."

. —M. Bendandi. (University Clinic of Navarre, Spain).

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."

. —Peter Chiba. (University of Vienna, Austria).

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."

. —Eduardo A. Castro. (INIFTA, Argentina).

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."

. —Kenji Hashimoto. (Chiba University, Japan).

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."

. —Daniel Shek. (Chinese University of Hong Kong, Hong Kong).

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."